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Neil poloso, Chau Vu, David F. Woodward; Prostaglandin E2 Sensitive Receptors Reduce Leukocyte Infiltration And Protein Exudation In Lps Induced Uveitis In Rats. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6271.
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Anterior uveitis can lead to potentially vision threatening conditions. Several models of uveitis in rodents have been used to characterize potential therapeutics. In this study we aimed to characterize the contribution of prostanoids to inflammation in an LPS-induced uveitis model in rats.
We employed the rat EIU(endotoxin-induced uveitis) model. All drugs and vehicle were applied to each eye in 10μl of volume. Prostanoid receptor agonists or vehicle were applied 1 hr before model induction (injection of LPS in the hind rear footpad) and applied twice during uveitis development (2 hr and 5hr). Rats were sacrificed at 18 hrs and aqueous humor was collected and pooled bilaterally. Inflammatory markers (Leukocyte infiltration and protein exudation) were measured using a hemocytometer and protein concentration, repectively. Additionally, cytokines present in the aqueous humor were measured as an another indicator of inflammation by Luminex.
The peak of leukocyte infiltration was determined experimentally to be 18-20 hrs. Given this data receptor agonists were given TID, with one dose being a pre-treatment. Initial studies showed no effect of the NSAID, Ketorolac (Acular). Based on this data we hypothesized that receptor agonists and not antagonists might be active in this model. PGE2 and selective receptor agonists Sulprostone (EP1,3), Butaprost (EP2), S(5)-[1 E.3S)-3-hydroxy-4-phenylbut-1-en-1-yl]-1 -[6-(1H-tetrzol-5-yl)hexyl] pyrrolidin-2-one (EP4) were applied topically at 0.1% as described above. All EP receptor agonists as well as PGE2 suppressed leukocyte infiltration in this model. However, only the EP 1,3 receptor agonist, Sulprostone, inhibited leukocyte infiltration, protein exudation and inflammatory cytokines (MCP-1, MIP-1α, RANTES, IL-6, and TNF-α).
Although the rat EIU model has been in use for decades, very little published data exists on the activity of prostanoid agonists or antagonists in this model. Surprisingly, we found that EP receptor agonists (even PGE2 itself), not antagonists are active in inhibiting multiple inflammatory markers induced in this model. This highlights that this model of uveitis is a useful tool in screening prostanoid agonists with potential anti-inflammatory properties.
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